Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
A recombinant measles virus vaccine strain rMV-Hu191 has oncolytic effect against human gastric cancer by inducing apoptotic cell death requiring integrity of lipid raft microdomains
Ist Teil von
Cancer letters, 2019-09, Vol.460, p.108-118
Ort / Verlag
Ireland: Elsevier B.V
Erscheinungsjahr
2019
Link zum Volltext
Quelle
Elsevier ScienceDirect Journals
Beschreibungen/Notizen
Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect.
•rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation in vitro.•rMV-Hu191 suppressed tumors growth and prolonged survival in vivo.•rMV-Hu191 induced caspase-dependent apoptosis both in vitro and in vivo.•Lipid rafts mediated rMV-Hu191 entry, but not for virus binding and replication.•Lipid rafts is required for induction of caspase-dependent apoptosis.